• Neurobiology of aging · Jun 2014

    Missense variant in TREML2 protects against Alzheimer's disease.

    • Bruno A Benitez, Sheng Chih Jin, Rita Guerreiro, Rob Graham, Jenny Lord, Denise Harold, Rebecca Sims, Jean-Charles Lambert, J Raphael Gibbs, Jose Bras, Celeste Sassi, Oscar Harari, Sarah Bertelsen, Michelle K Lupton, John Powell, Celine Bellenguez, Kristelle Brown, Christopher Medway, Patrick C G Haddick, Marcel P van der Brug, Tushar Bhangale, Ward Ortmann, Tim Behrens, Richard Mayeux, Margaret A Pericak-Vance, Lindsay A Farrer, Gerard D Schellenberg, Jonathan L Haines, Jim Turton, Anne Braae, Imelda Barber, Anne M Fagan, David M Holtzman, John C Morris, 3C Study Group, EADI consortium, Alzheimer's Disease Genetic Consortium (ADGC), Alzheimer's Disease Neuroimaging Initiative (ADNI), GERAD Consortium, Julie Williams, John S K Kauwe, Philippe Amouyel, Kevin Morgan, Andy Singleton, John Hardy, Alison M Goate, and Carlos Cruchaga.
    • Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
    • Neurobiol. Aging. 2014 Jun 1;35(6):1510.e19-26.

    AbstractTREM and TREM-like receptors are a structurally similar protein family encoded by genes clustered on chromosome 6p21.11. Recent studies have identified a rare coding variant (p.R47H) in TREM2 that confers a high risk for Alzheimer's disease (AD). In addition, common single nucleotide polymorphisms in this genomic region are associated with cerebrospinal fluid biomarkers for AD and a common intergenic variant found near the TREML2 gene has been identified to be protective for AD. However, little is known about the functional variant underlying the latter association or its relationship with the p.R47H. Here, we report comprehensive analyses using whole-exome sequencing data, cerebrospinal fluid biomarker analyses, meta-analyses (16,254 cases and 20,052 controls) and cell-based functional studies to support the role of the TREML2 coding missense variant p.S144G (rs3747742) as a potential driver of the meta-analysis AD-associated genome-wide association studies signal. Additionally, we demonstrate that the protective role of TREML2 in AD is independent of the role of TREM2 gene as a risk factor for AD.Copyright © 2014 Elsevier Inc. All rights reserved.

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